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Tracing Flu Infections in Mice

Scientists have successfully tracked the progression of influenza
virus infections within the lungs of mice. The accomplishment will
lead to a better understanding of how flu infections spread and
may suggest new strategies for combating them.

Influenza A virus, the type of flu that causes most seasonal
and pandemic outbreaks, has been studied extensively in animal
models and tissue cultures. However, the way it moves through the
human respiratory system and infects cells isn’t well known.
A major barrier to uncovering the course of infection has been
the difficulty in visualizing viruses within the body (in vivo).

A team of researchers led by Dr. Adolfo García-Sastre
at the Mount Sinai School of Medicine set out to express a reporter
gene in influenza viruses that could be used to track their movement
in vivo. Their work was supported by NIH’s National Institute
of Allergy and Infectious Diseases (NIAID).

In the online early edition of Proceedings of the National
Academy of Sciences on June 7, 2010, the team reported creating
a recombinant influenza A strain carrying a green fluorescent
protein (GFP) reporter gene. The reporter gene was placed in
the NS segment of the influenza genome.

The new NS1-GFP virus infected and replicated well in mouse lungs,
although it was less pathogenic than the wild type virus, the form
that typically occurs in nature. Using the fluorescence as a marker,
the researchers traced the course of infection in mouse lungs and
found that it started in areas close to the large airways (near
the trachea) and later spread to deeper sections of the lungs.
In addition to epithelial cells, a large proportion of immune cells
were GFP positive, suggesting active infection of these cells.

The scientists tested the effects of 2 influenza inhibitors on
the movements of the virus. Treatment with oseltamivir dramatically
reduced influenza infection in all cell types. Amantadine treatment
more efficiently blocked infection in specific immune cells.

The new NS1-GFP strain can be used in future studies to answer
new research questions. “This system will allow researchers
to easily track viruses during immune responses, as well as to
quickly evaluate the impact of potential therapies on influenza
pathogenesis,” García-Sastre says.